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Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice

(2019) METALLOMICS. 11(6). p.1093-1103
Author
Organization
Abstract
Patients with chronic liver disease from different aetiologies show a light serum Cu isotopic composition compared to the reference population, with the enrichment in the Cu-63 isotope correlating with the severity of the disease. However, the mechanisms underlying Cu isotope fractionation at the onset and during progression of the disease are still unclear. In this work, a common bile duct ligation (CBDL) murine model was used to investigate the effect of cholestasis-induced liver disease on the Cu isotopic composition. Wild type male and female mice underwent surgical ligation of the common bile duct and were sacrificed 2, 4 and 6 weeks, and 4, 6 and 8 weeks after the surgical intervention, respectively. The age- and gender-matched control mice underwent sham surgery. Disease progression was evaluated using serum bilirubin levels, hepatic pro-inflammatory chemokine levels and Metavir fibrosis score. CBDL-operated mice show an overall body enrichment in the light isotope Cu-63. The Cu isotopic composition of organs, bone and serum becomes gradually lighter compared to the sham-operated mice with increasing severity of the disease. The light Cu isotopic composition of the CBDL-operated mice might result from an altered Cu intake and/or excretion. As the intestinal uptake of dietary Cu is largely mediated by transporters of Cu(i), mRNA and protein expression levels of two major metal transporters (CTR1 and DMT1) and Cu reductases (STEAP proteins and duodenal cytochrome B) were examined in the duodenal tissues as potential factors inducing Cu isotope fractionation. However, no significant differences in protein expression levels were observed between the CBDL- and sham-operated mice.
Keywords
ICP-MASS SPECTROMETRY, BLOOD-SERUM, HEPATOCELLULAR-CARCINOMA, TRANSPORTER CTR1, CU, EXPRESSION, FRACTIONATION, INFLAMMATION, EXCRETION, DIAGNOSIS

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MLA
Costas Rodriguez, Marta et al. “Body Distribution of Stable Copper Isotopes During the Progression of Cholestatic Liver Disease Induced by Common Bile Duct Ligation in Mice.” METALLOMICS 11.6 (2019): 1093–1103. Print.
APA
Costas Rodriguez, M., Van Campenhout, S., Hastuti, A. A. M. B., Devisscher, L., Van Vlierberghe, H., & Vanhaecke, F. (2019). Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice. METALLOMICS, 11(6), 1093–1103.
Chicago author-date
Costas Rodriguez, Marta, Sanne Van Campenhout, Agustina Ari Murti Budi Hastuti, Lindsey Devisscher, Hans Van Vlierberghe, and Frank Vanhaecke. 2019. “Body Distribution of Stable Copper Isotopes During the Progression of Cholestatic Liver Disease Induced by Common Bile Duct Ligation in Mice.” Metallomics 11 (6): 1093–1103.
Chicago author-date (all authors)
Costas Rodriguez, Marta, Sanne Van Campenhout, Agustina Ari Murti Budi Hastuti, Lindsey Devisscher, Hans Van Vlierberghe, and Frank Vanhaecke. 2019. “Body Distribution of Stable Copper Isotopes During the Progression of Cholestatic Liver Disease Induced by Common Bile Duct Ligation in Mice.” Metallomics 11 (6): 1093–1103.
Vancouver
1.
Costas Rodriguez M, Van Campenhout S, Hastuti AAMB, Devisscher L, Van Vlierberghe H, Vanhaecke F. Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice. METALLOMICS. 2019;11(6):1093–103.
IEEE
[1]
M. Costas Rodriguez, S. Van Campenhout, A. A. M. B. Hastuti, L. Devisscher, H. Van Vlierberghe, and F. Vanhaecke, “Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice,” METALLOMICS, vol. 11, no. 6, pp. 1093–1103, 2019.
@article{8626922,
  abstract     = {Patients with chronic liver disease from different aetiologies show a light serum Cu isotopic composition compared to the reference population, with the enrichment in the Cu-63 isotope correlating with the severity of the disease. However, the mechanisms underlying Cu isotope fractionation at the onset and during progression of the disease are still unclear. In this work, a common bile duct ligation (CBDL) murine model was used to investigate the effect of cholestasis-induced liver disease on the Cu isotopic composition. Wild type male and female mice underwent surgical ligation of the common bile duct and were sacrificed 2, 4 and 6 weeks, and 4, 6 and 8 weeks after the surgical intervention, respectively. The age- and gender-matched control mice underwent sham surgery. Disease progression was evaluated using serum bilirubin levels, hepatic pro-inflammatory chemokine levels and Metavir fibrosis score. CBDL-operated mice show an overall body enrichment in the light isotope Cu-63. The Cu isotopic composition of organs, bone and serum becomes gradually lighter compared to the sham-operated mice with increasing severity of the disease. The light Cu isotopic composition of the CBDL-operated mice might result from an altered Cu intake and/or excretion. As the intestinal uptake of dietary Cu is largely mediated by transporters of Cu(i), mRNA and protein expression levels of two major metal transporters (CTR1 and DMT1) and Cu reductases (STEAP proteins and duodenal cytochrome B) were examined in the duodenal tissues as potential factors inducing Cu isotope fractionation. However, no significant differences in protein expression levels were observed between the CBDL- and sham-operated mice.},
  author       = {Costas Rodriguez, Marta and Van Campenhout, Sanne and Hastuti, Agustina Ari Murti Budi and Devisscher, Lindsey and Van Vlierberghe, Hans and Vanhaecke, Frank},
  issn         = {1756-5901},
  journal      = {METALLOMICS},
  keywords     = {ICP-MASS SPECTROMETRY,BLOOD-SERUM,HEPATOCELLULAR-CARCINOMA,TRANSPORTER CTR1,CU,EXPRESSION,FRACTIONATION,INFLAMMATION,EXCRETION,DIAGNOSIS},
  language     = {eng},
  number       = {6},
  pages        = {1093--1103},
  title        = {Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice},
  url          = {http://dx.doi.org/10.1039/c8mt00362a},
  volume       = {11},
  year         = {2019},
}

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